We have now established that cyclic AMP concentration in axotomized frog neurons is initially increased (at 6-7 days after transecting a lumbar spinal nerve), and subsequently decreased (beginning at 21 days). Cyclic AMP concentration remains depressed until monosynaptic reflex connections begin to be re-established. We are currently attempting to determine if an increase in cyclic AMP concentration and synaptic reorganization are related events. We also are investigating the dynamic aspects of cyclic nucleotide concentration changes by measuring adenyl cyclase and phosphodiesterase activities in spinal nerves and segments following axotomy. We are measuring the axonal transport of these enzymes in normal and axotomized spinal nerves. In addition, we are investigating the possible association of cyclic nucleotides with synaptic transmission in the normal frog spinal cord, including the ability of several putative transmitters to stimulate adenyl cyclase extracted from the ventral horn of lumbar spinal segments. Furthermore, we have preliminary data indicating that various phenomena associated with axon-transection are temperature dependent. We are raising colonies of frogs at different environmental temperatures, transecting lumbar spinal nerves and following the time course of several events associated with axotomy.